Tick-Borne Encephalitis (TBE)

 

 

 

1.                Synonyms for TBE

 

v                             Central European encephalitis

v                             Russian spring-summer encephalitis

                  (Western and Eastern subtypes)

v                             Far East Russian encephalitis

v                             Biundulating meningo-encephalitis

v                             Diphasic milk fever (biphasic)

v                             Kumlinge disease

v                             Schneider’s disease

 

 

2.                Causative Agent

 

Flavivirus (+RNA) belonging to the family flaviviridae transmitted by infected ticks.  Due to this specific route of transmission by infected ticks, it is also called an arbovirus (arthropod-borne).

 

3.                Incubation Period

 

7-14 days prior to the onset of the first stage, but may last from 2 to 28 days.

 

 

4.                Risk to the Traveller

 

The precise risk to the traveller is unknown.

 

 

 

 

 

4.1             Incidence:

 

Endemic areas in:

 

            Germany                    -           1:900

            Sweden                      -           1:600 (following a tick bite)

 

 

4.2             Morbidity

 

Endemic areas in Austria:

            General population                           18 - 30/100,000

 

Forestry Workers in:

Austria                                                98 -100/100,000

Former Czechoslovakia                      1-  16/100,000

Former USSR                                     5 -  46/100,000

Former Yugoslavia                                      2/100,000

 

 

4.3             Mortality

 

General          1-2%

Far East         23-24%

 

 

5.                Transmission

 

5.1       Associated with Vectors

 

The disease agent, i.e. the TBE virus (TBEV) is transmitted to man by tick bites. The ticks’ ability to feed on the blood of a variety of host animals and to adapt to domestic animal species, as well as their long life cycle make them ideal vectors for a variety of pathogens.

Between 0.1 – 10% of ticks are infected in endemic areas.

In Central Europe, 8 species of “hard” ticks (having a dorsal shield) have been identified so far, by which TBE virus may be transmitted.

-          Ixodes ricinus (castor-bean tick) is chief vector in Europe (Western type)

-          Ixodes persulcatus for Far Eastern subtype

-          Ixodes hexagonus

-          Ixodes arboricola

-          Haemaphysilis punctata

-          Haemaphysilis concinna

-          Dermacentor marginatus

-          Dermacentor reticulatus

 

Female ticks usually transmit the virus to a single host only. Male ticks feed more often and in this way may infect several vertebrates.

Wet summers and mild winters tend to increase the tick population density.

Ticks themselves do not develop the disease. The virus hibernates in ticks – once a tick is infected, it carries the virus for life.

40% of victims have no recollection of having been bitten by a tick.

 

5.2       Association with Ingestion of Milk

 

Infection by the alimentary route as a result of the ingestion of raw milk is possible (Slovakia, Poland and former Yugoslavia). However, this route of infection is not believed to play any role in Austria and other West European countries. This includes milk from goats, cows, and sheep, or cheeses made from raw milk.

One person got the disease after slaughtering a goat that had probably been in the viremic stage.

Laboratory infections have like-wise been reported.

 

5.3       Association with Person-to-Person Contact

 

Although it has not been observed, man to man transmission is a theoretical possibility, e.g. when blood from a viremic patient is transfused to a healthy person.

 

5.4       Natural Foci

 

The virus persists in so-called natural foci, where it circulates among verbebrate hosts (mainly rodents) and the arthropod host (ticks). The virus can be transmitted to man or other hosts by larvae, nymphs, or adult ticks.

5.4.1   Factors affecting the formation of natural foci:

 

-     Population density and dynamics of infected ticks and their hosts

-     Susceptibility of individual hosts

-     Proportion of immune hosts

-     Temperature (7ο C)

-     Relative humidity (+ 92%)

-     Soil humidity

-     Biotype (see geographical risk)

TBEV is transferred to the host with the saliva of an infected tick; at the same time TBEV contained in host tissue enters the tick’s intestine with blood feeding.  The tick feeds for a maximum of 15 minutes.

For most hosts, TBEV is apathogenic. An infected host develops specific antibodies to the TBEV and then remains immune for life to reinfection.

 

1.                Geographic Considerations

 

Covers almost the entire southern part of the non-tropical Eurasian forest belt, from Alsace-Lorraine in the West to Vladivostok and the northern and eastern regions of China in the East.

In several European states no TBE cases have been reported yet; among these are Great Britain, Ireland, Iceland, Belgium, the Netherlands, Luxembourg, Spain or Portugal (1999).

 

Seasonal peaks of disease incidence in early summer (June, July, August).  Sometimes a second peak in October. Sites localized in transitional zones between different forms of vegetation – forest fringes with adjacent grassland, glades, riverside meadows and marshlands, forest plantation with brushwood and shrubbery – situated on sunny slopes facing south, at altitudes up to 1,000 metres. Such rural landscapes, especially when benches, cross-country tracks or barbeque pits are provided, attract many people.

 

 

2.                Signs and Symptoms

 

The clinical picture of TBE is characterized by a biphasic/diphasic course. The clinically silent incubation period is followed by elevated temperature and an asymptomatic interval with remission of fever and symptoms.  The second phase is characterized by another sudden rise in temperature.

70% of those infected can be inapparent or only in the mild 1st phase.

First Stage:         2-4 days (1-8) – viraemic phase

Flu-like symptoms: fatigue, headache, aching back and limbs, catarrhal symptoms of upper airways, GI symptoms, anorexia, nausea, fever.

Asymptomatic Interval:           8 days (1-20)

Second Stage:  2-4 weeks after infection

                              20-30% of those infected go on to the 2nd phase.

Involves CNS: meningitis (45%), encephalitis, meningo-encephalitis (50%), meningo-encephaloradiculitis (5%).

Hospitalization usually required for 3 weeks – but it may last longer, sometimes years (depending on sequelae).

Incidence of sequelae varies from 6-46%. This includes:

Neuro-psychiatric (10-20%)

-           Headache

-           Lack of concentration

-           Depression

-           Dissolves of the automatic nervous system

-           Hearing impairment

-           Mood disorders

Residual paresis and atrophies (3-11%)

Rarely severe in children less than 4 years.

 

 

3.                Prevention

 

 

3.1             Control of the tick population

Do not produce the desired effect, as the virus persists not only in ticks but also in wild animals.

 

3.2             Protective clothes and repellents

Solid footwear, socks, close-fitting trousers, smooth fabrics, etc. may help to make access to the skin more difficult for ticks.

Light-colored clothing to facilitate finding and removing ticks.

Insect repellents such as DEET and permethrin (body and/or clothes).

Full body check for ticks and removal of ticks.

 

 

 

3.3             Marking of endemic areas by warning signs

 

3.4             Avoid drinking raw milk and its products

 

3.5             Active immunization

 

3.5.1       Types of Vaccines

 

 

3.5.1.1FSME – IMMUN Inject-injector(Baxter-Immuno Behring)

Whole-virus vaccine inactivated by formaldehyde and cultured in chick embryo cells.

FSME  0.5 ml i.m.

Dose 1:          0 months

Dose 2:          1-3 months after 1st dose (Can be shortened to 2 weeks            )

Dose 3:          9-12 months after second dose.

If the third dose is given before the recommended 9-12 months after the second dose, an additional dose must be given 9-12 months after the second dose.

Second dose should be given 2 weeks before departure.

Booster after 3 years.  Protection lasts for 3 years.

Should a tick bite occur between doses 1 and 2, and more than 4 days has passed since the first dose, the second dose should be administered immediately.  The third dose should be administered at the time specified in the immunization schedule.

Accelerated Schedule:

Dose 1:          0 days

Dose 2:          14 days

Dose 3:          1 year

Booster:         Every 3 years

                        Seroconversion 98-99%

 

      After dose 1 >70%

      After dose 2 >95%    Measured 1 month after                                                       immunization

After dose 3 >99%

      After dose 1 >40%

      After dose 2 >53%    12 months after immunization

After dose 3                   >79%

 

Protection rate >98% after 3 doses, and >90% after 2 doses.

 

3.5.1.2Encepur (Chiron Behring)

Inactivated vaccine

0.5 ml i.m.

Standard Schedule:

                  Dose 1:          0 months

Dose 2:          1-3 months after 1st dose (Can be shortened to 2 weeks)

Dose 3:          9-12 months after second dose.

Booster after 3 years

Accelerated schedule possible:

Dose 1:          0 days

Dose 2:          14 days

Dose 3:          1 year

Booster:         Every 3 years

These vaccines are not licensed in Canada and individual requests need to be placed with the Bureau of Biologics, Health Canada (613) 941-2114. Distributor is Immuno-Canada 1-800-551-0478

 

3.6             Passive Immunization:

Only in persons > 14 years.

Should receive it within 4 days after a tick bite

1-2 days 0.1 ml/kg body weight

3-4 days 0.2 ml/kg body weight

If TBE immuneglobulin has been received, it is recommended to leave an interval of 4 weeks before vaccine is given.

 

 

9.      Diagnosis:

 

IgG  and IgM ELISA (Baxter-Immuno)

            Serology: Almost always detectable at the onset of the 2nd phase.

            CSF: Not always detectable.

 

Virus identification only before sero-conversion and in post-mortem material successful

 

        Electron-microscopy

        Cultivation

 

 

10.    Treatment:

 

TBE is a viral disease of the central nervous system for which no effective therapy exists.

 

 

11.    Indications for Vaccination:

 

People at high risk for contracting it, such as travellers or residents of high-risk areas.

April – August (sometimes till October) is high risk time period

Also take into consideration:

-                                  Length of stay (longer than 3 weeks)

-                                  Place of residence (urban or rural)

-                                  Visit endemic area

-                                  Camping, hiking

Travellers with extensive, unprotected outdoor, evening or nighttime exposure in rural areas might be at high risk even if the trip is brief.

 

 

12.   Warnings/Precautions/Contraindications against

Vaccination

 

 

12.1         Warnings

Individuals with a suppressed immune system may not produce an adequate immune response.

 

12.2         Precautions

Moderate to severe illness with or without fever

Allergies to components of the vaccine (e.g. formaldehyde) or egg white constitute relative contraindications.

 

12.3         Contraindication

Anaphylaxis to components of the vaccine.

Anaphylaxis to a previous dose of this vaccine

Not to be used in children under 12 years of age (Encepur)

No information available on the safety of these vaccines during pregnancy and breastfeeding and should be used with caution, and only if the benefit outweighs any potential risk to the infant.

 

 

13.    Adverse Effects

 

Headache, fever (pyrexia), pins and needles (parasthesia), nausea and vomiting, pain in the joints (arthralgia), pain in the muscles (myalgia), pain and swelling at site of injection.

Warning from Health Canada:

Human serum albumin (HAS) used as a stabilizer in the vaccine (FSME-IMMUN®), was prepared from plasma collected from European donors.  These donors are properly screened according to European guidelines and criteria, and the product is marketed and commonly used in Europe.  However, due to the prevalence of Bovine Spongiform Encephalopathy (BSE) in European countries, there is a theoretical possibility that donors living in these countries may be silent carriers of prion agents through their exposure to BSE infected beef products.

The theoretical risk of vCJD to the Canadian population for vaccines manufactured with human albumin has been estimated by the Population and Public Health Branch of Health Canada to be 1 in 100-million per treatment per subject vaccinated.

 

14.    Storage and Administration

 

Shelf life – 1 year

 

Store between 2-8 °C

 

 

15.    References

 

1.                  Caumes E.  Health and Travel.  Aventis Pasteur. 2000

2.                  Dawood R.  Travellers’ Health. How to stay healthy abroad.  Oxford University Press.  2002

3.                  DuPont HL, Steffen R.  Textbook of Travel Medicine and Health.  Second Edition.  BC Decker Inc, Hamilton, London.  2001

4.                  FSME-Immun Inject product monograph, February 2000

5.                  International Scientific Working Group on TBE Website.  http://www4.tbe-info.com

6.                  Tick-Borne Encephalitis (TBE) and its Immunoprophylaxis.  Baxter.  January 1999.

 

7.                  Thompson RF.  Travel & Routine Immunizations.  A Practical Guide for the Medical Office.  Shoreland, 2002

 

8.                  Wise, M.  The Travel Doctor.  Your guide to staying healthy while you travel.  Firefly Books.  2002

 

9.                  World Health Organization/International Travel and Health.  2002

 

 

Contributor:

Dr Tania Diener

Executive Director/Medical Health Officer

Population and Public Health Services

Regina Qu'Appelle Health Region

2110 Hamilton Street

Regina

Saskatchewan

S4P 2E3

Canada

Tel: (306) 766-7774

Fax: (306) 766-7607

E-Mail: Tania.Diener@rqhealth.ca